Cartilage Oligomeric Matrix Protein (COMP) and its Important Functions

Cartilage matrix oligomeric protein (COMP) is an important extracellular matrix glycoprotein (ECM) originally isolated from cartilage but has since been found in a variety of tissues, including tendons, ligaments, and connective tissue. Its main functions involve mediating the interaction of cells and extracellular matrix, enhancing the mechanical strength of tissues, and regulating the secretion of collagen and other ECM proteins.

The article examines in detail the multiple roles of COMP in physiological and pathological conditions, focusing on diseases resulting from COMP mutations, known as COMPopathies, and various chronic conditions such as fibrosis, cardiomyopathy, and cancer. Impaired regulation of COMP has been associated with osteoarthritis, rheumatoid arthritis, and other conditions involving wear and tear of cartilage and tissue.

1. Functions of COMP

COMP, a member of the thrombospondin family, is a polymeric protein involved in forming the extracellular matrix and the interaction between proteins and cells. It consists of five units, each with specialized building blocks linked to calcium. This structure is essential for adequately folding the protein and its integration into the extracellular matrix. Under normal conditions, COMP is involved in collagen secretion, the organization of collagen fibrils, and the mechanical strengthening of tissues, mainly cartilage and tendons.

In addition to its mechanical function, COMP has been found to regulate the promotion of cell growth, particularly chondrocytes. It enhances chondrocyte proliferation and extracellular matrix production through its interaction with proteins such as GEP (Granulin-Epithelin Precursor). This function is critical for properly developing and maintaining cartilage, while its disruption leads to severe diseases such as pseudoachondroplasia.

2. COMPopathies: Pseudoachondroplasia and Multiple Epiphyseal Dysplasia

Mutations in COMP cause two primary genetic disorders: pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). These disorders are known as COMPopathies and are caused by autosomal dominant mutations that disrupt COMP's ability to fold and integrate properly into the extracellular matrix. Most of the mutations are located in the protein regions that bind calcium, resulting in COMP's retention in the endoplasmic reticulum of chondrocytes.

Pseudoachondroplasia is a severe form of dwarfism characterized by a significant decrease in bone growth and extensive abnormalities in the joints. Symptoms include slowed growth during the first few years of life, wide and loose joints, and frequent arthritis at a young age. Patients often need joint surgery in adulthood, while osteoarthritis is a common complication.

Multiple epiphyseal dysplasia is a milder form of the disease, with less severe dwarfism and less pronounced joint symptoms. Although MED is milder than PSACH, it still causes significant joint development and functionality problems, as well as

3. Fibrous Diseases and the Role of COMP

Fibrosis, characterized by excessive accumulation of extracellular matter, is also associated with the expression of COMP. This protein plays a role in the organization of type I collagen and other extracellular matrix elements, increasing tissue hardness, which is critical in the progression of fibrotic disorders such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (scleroderma). In these diseases, COMP works with TGF-β, an essential protein that promotes the conversion of fibroblasts into myofibroblasts, leading to increased collagen production and other processes that harden tissues.

In cutaneous fibrosis, COMP appears to regulate the production of collagen and other extracellular matrix components, contributing to tissue stability and enhancing fibrotic processes. In the lungs, increased expression of COMP is associated with more severe fibrosis and decreased respiratory capacity, making it a potential therapeutic target for patients with pulmonary fibrosis.

4. Cancer and COMP

In addition to its role in the extracellular matrix, COMP has been shown to play a critical role in cancer progression. Elevated concentrations of COMP have been observed in various types of cancer, such as breast and prostate cancer. In cancer, COMP enhances the invasion of cancer cells and contributes to cell migration, which leads to increased malignancy and metastasis.

An impressive element is that COMP promotes cancer cells' resistance to endoplasmic reticulum stress, giving them a survival advantage in low-oxygen environments, which are characteristic of internal tumors. This function is particularly evident in studies showing that COMP expression is associated with reducing cancer cell apoptosis, thereby promoting more significant tumor growth and increased aggressiveness.

5. Cardiomyopathy and Relationship with COMP

Dilated cardiomyopathy (DCM), a severe form of heart failure, has also been linked to COMP. Loss of COMP reduces the stability of connections between myocardial cells and the extracellular matrix, which leads to impaired heart function and

In experimental models, myocardial cells lacking COMP cannot withstand the mechanical stress of cardiac function. COMP decline in dilated cardiomyopathy is also associated with increased expression of proteins such as MMP-9, which promote extracellular matrix degradation, further exacerbating heart failure.

6. Biomarker and Therapeutic Goal

COMP is a reliable biomarker for diseases involving cartilage and extracellular matrix destruction, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Serum and synovial fluid levels of COMP are higher in people with early osteoarthritis and rheumatoid arthritis, and are associated with disease progression and cartilage destruction.

COMP can be used as an indicator of inflammation and joint destruction in conditions such as rheumatoid arthritis. Elevated serum COMP levels are associated with increased joint destruction, while lower levels are associated with milder forms of the disease. In osteoarthritis, COMP levels predict disease progression and guide therapeutic interventions.

Conclusions and Future Prospects

Cartilage matrix oligomeric protein (COMP) is a multidimensional protein involved in multiple physiological and pathological processes. COMP is a critical component of the extracellular matrix, from the skeleton and integrity of cartilage to its involvement in severe conditions such as cancer and fibrosis.

Future research is focused on developing new therapeutic approaches that target COMP, either to prevent cartilage destruction in diseases such as osteoarthritis or to suppress the aggressiveness of cancer cells. Concentrating on how COMP interacts with other proteins and cell receptors may lead to the development of new treatments for various conditions.

See the test: Cartilage Matrix Oligomeric Protein (COMP), Serum